WO2014130671A8 - Mice expressing humanized t-cell co-receptors - Google Patents

Mice expressing humanized t-cell co-receptors Download PDF

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Publication number
WO2014130671A8
WO2014130671A8 PCT/US2014/017395 US2014017395W WO2014130671A8 WO 2014130671 A8 WO2014130671 A8 WO 2014130671A8 US 2014017395 W US2014017395 W US 2014017395W WO 2014130671 A8 WO2014130671 A8 WO 2014130671A8
Authority
WO
WIPO (PCT)
Prior art keywords
cell
receptors
mice expressing
expressing humanized
human
Prior art date
Application number
PCT/US2014/017395
Other languages
French (fr)
Other versions
WO2014130671A1 (en
Inventor
Lynn Macdonald
Andrew J. Murphy
Naxin Tu
Vera VORONINA
Cagan Gurer
Original Assignee
Regeneron Pharmaceuticals, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to EP14708430.5A priority Critical patent/EP2958938B1/en
Priority to SI201431279T priority patent/SI2958938T1/en
Application filed by Regeneron Pharmaceuticals, Inc. filed Critical Regeneron Pharmaceuticals, Inc.
Priority to CN201480021698.3A priority patent/CN105164153B/en
Priority to LTEP14708430.5T priority patent/LT2958938T/en
Priority to KR1020217032326A priority patent/KR102369454B1/en
Priority to RS20190870A priority patent/RS58962B1/en
Priority to KR1020237031201A priority patent/KR20230135166A/en
Priority to PL14708430T priority patent/PL2958938T3/en
Priority to CA2900832A priority patent/CA2900832A1/en
Priority to AU2014218897A priority patent/AU2014218897C1/en
Priority to EP19159217.9A priority patent/EP3543253B1/en
Priority to KR1020157025675A priority patent/KR102313047B1/en
Priority to EP24155637.2A priority patent/EP4374690A2/en
Priority to DK14708430.5T priority patent/DK2958938T3/en
Priority to KR1020227006387A priority patent/KR102579405B1/en
Priority to JP2015558224A priority patent/JP6444895B2/en
Priority to ES14708430T priority patent/ES2736052T3/en
Publication of WO2014130671A1 publication Critical patent/WO2014130671A1/en
Publication of WO2014130671A8 publication Critical patent/WO2014130671A8/en
Priority to HK16101695.8A priority patent/HK1213908A1/en
Priority to AU2018271383A priority patent/AU2018271383B2/en
Priority to CY20191100749T priority patent/CY1121979T1/en
Priority to HRP20191280TT priority patent/HRP20191280T1/en
Priority to AU2021290271A priority patent/AU2021290271A1/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70514—CD4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70517—CD8
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0603—Embryonic cells ; Embryoid bodies
    • C12N5/0606—Pluripotent embryonic cells, e.g. embryonic stem cells [ES]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70539—MHC-molecules, e.g. HLA-molecules
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • C12N2015/8527—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic for producing animal models, e.g. for tests or diseases
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2517/00—Cells related to new breeds of animals
    • C12N2517/02—Cells from transgenic animals

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Toxicology (AREA)
  • Environmental Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Developmental Biology & Embryology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Reproductive Health (AREA)
  • Hematology (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Steroid Compounds (AREA)

Abstract

The invention provides genetically modified non-human animals that express chimeric human/non-human T cell co-receptor polypeptides (e.g., CD4, CD8α, CD8β ), as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same.
PCT/US2014/017395 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors WO2014130671A1 (en)

Priority Applications (22)

Application Number Priority Date Filing Date Title
EP24155637.2A EP4374690A2 (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors
KR1020157025675A KR102313047B1 (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors
CN201480021698.3A CN105164153B (en) 2013-02-20 2014-02-20 Humanized T cell co-receptor mice
SI201431279T SI2958938T1 (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors
KR1020217032326A KR102369454B1 (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors
RS20190870A RS58962B1 (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors
DK14708430.5T DK2958938T3 (en) 2013-02-20 2014-02-20 Mice expressing humanized T cell co-receptors
PL14708430T PL2958938T3 (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors
CA2900832A CA2900832A1 (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors
AU2014218897A AU2014218897C1 (en) 2013-02-20 2014-02-20 Mice expressing humanized T-cell co-receptors
EP19159217.9A EP3543253B1 (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors
EP14708430.5A EP2958938B1 (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors
LTEP14708430.5T LT2958938T (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors
KR1020237031201A KR20230135166A (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors
KR1020227006387A KR102579405B1 (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors
JP2015558224A JP6444895B2 (en) 2013-02-20 2014-02-20 Mice expressing humanized T cell co-receptors
ES14708430T ES2736052T3 (en) 2013-02-20 2014-02-20 Mice expressing humanized T-cell co-receptors
HK16101695.8A HK1213908A1 (en) 2013-02-20 2016-02-17 Mice expressing humanized -cell co-receptors
AU2018271383A AU2018271383B2 (en) 2013-02-20 2018-11-30 Mice expressing humanized t-cell co-receptors
CY20191100749T CY1121979T1 (en) 2013-02-20 2019-07-12 MICE EXPRESSING HUMANIZED T-LYMPHO CELL CO-RECEPTORS
HRP20191280TT HRP20191280T1 (en) 2013-02-20 2019-07-16 Mice expressing humanized t-cell co-receptors
AU2021290271A AU2021290271A1 (en) 2013-02-20 2021-12-22 Mice expressing humanized t-cell co-receptors

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201361766762P 2013-02-20 2013-02-20
US61/766,762 2013-02-20
US201361890915P 2013-10-15 2013-10-15
US61/890,915 2013-10-15

Publications (2)

Publication Number Publication Date
WO2014130671A1 WO2014130671A1 (en) 2014-08-28
WO2014130671A8 true WO2014130671A8 (en) 2015-10-01

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PCT/US2014/017395 WO2014130671A1 (en) 2013-02-20 2014-02-20 Mice expressing humanized t-cell co-receptors

Country Status (19)

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US (3) US9848587B2 (en)
EP (3) EP3543253B1 (en)
JP (5) JP6444895B2 (en)
KR (4) KR20230135166A (en)
CN (2) CN111484999A (en)
AU (3) AU2014218897C1 (en)
CA (1) CA2900832A1 (en)
CY (1) CY1121979T1 (en)
DK (1) DK2958938T3 (en)
ES (1) ES2736052T3 (en)
HK (1) HK1213908A1 (en)
HR (1) HRP20191280T1 (en)
HU (1) HUE045478T2 (en)
LT (1) LT2958938T (en)
PL (1) PL2958938T3 (en)
PT (1) PT2958938T (en)
RS (1) RS58962B1 (en)
SI (1) SI2958938T1 (en)
WO (1) WO2014130671A1 (en)

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JP7145920B2 (en) 2014-12-09 2022-10-03 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Non-human animals having humanized differentiation antigen group 274 genes

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US9043996B2 (en) 2011-10-28 2015-06-02 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex animals
PL3262932T3 (en) 2011-10-28 2019-10-31 Regeneron Pharma Genetically modified major histocompatibility complex mice
US9591835B2 (en) 2011-10-28 2017-03-14 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex animals
CN104039133B (en) 2011-10-28 2018-05-04 瑞泽恩制药公司 The genetic modification mouse of chimeric major histocompatibility complex (MHC) the II quasi-molecules of expression
KR20230135166A (en) * 2013-02-20 2023-09-22 리제너론 파아마슈티컬스, 인크. Mice expressing humanized t-cell co-receptors
JP6444321B2 (en) 2013-02-22 2018-12-26 リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Mice expressing humanized major histocompatibility gene complex
US20150342163A1 (en) 2013-02-22 2015-12-03 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex mice
EP4269430A3 (en) 2013-09-23 2024-01-10 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized signal-regulatory protein gene
RU2700484C2 (en) 2014-04-08 2019-09-17 Регенерон Фармасьютикалз, Инк. NON-HUMAN ANIMALS HAVING HUMANIZED Fc-γ-RECEPTORS
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MX2016016903A (en) 2014-06-19 2017-03-27 Regeneron Pharma Non-human animals having a humanized programmed cell death 1 gene.
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IL286414B2 (en) * 2014-11-24 2024-04-01 Regeneron Pharma Non-human animals expressing humanized cd3 complex
IL286403B2 (en) 2014-12-05 2023-10-01 Regeneron Pharma Non-human animals having a humanized cluster of differentiation 47 gene
MX2017012829A (en) * 2015-04-06 2018-02-23 Regeneron Pharma Humanized t cell mediated immune responses in non-human animals.
MA44907A (en) * 2015-09-11 2018-07-18 Agenus Inc GENETICALLY MODIFIED HOST CELLS AND THEIR METHODS OF USE
RU2745403C2 (en) 2015-11-20 2021-03-24 Регенерон Фармасьютикалз, Инк. Non-human animals having humanized lymphocyte-activation gene 3
WO2017150763A1 (en) * 2016-02-29 2017-09-08 (주)메디톡스 Animal model expressing human cd3 and use thereof
DK3422845T3 (en) 2016-02-29 2021-08-30 Regeneron Pharma GNAGER WITH A HUMANIZED TMPRSS GENE
WO2017210586A1 (en) 2016-06-03 2017-12-07 Regeneron Pharmaceuticals, Inc. Non-human animals expressing exogenous terminal deoxynucleotidyltransferase
IL274740B2 (en) 2017-11-30 2024-06-01 Regeneron Pharma Non-human animals comprising a humanized trkb locus
MA52177A (en) 2018-03-26 2021-02-17 Regeneron Pharma HUMANIZED RODENTS TO TEST THERAPEUTIC AGENTS
JP2021522208A (en) * 2018-04-19 2021-08-30 ベイラー カレッジ オブ メディスンＢａｙｌｏｒ Ｃｏｌｌｅｇｅ Ｏｆ Ｍｅｄｉｃｉｎｅ Reprogramming CD4 T cells into cytotoxic CD8 cells by forced expression of CD8ab and class 1 restricted T cell receptors
JP2021530970A (en) 2018-07-16 2021-11-18 リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. DITRA non-human animal model and its use
WO2022212582A1 (en) 2021-03-31 2022-10-06 Regeneron Pharmaceuticals, Inc. Genetically modified mice comprising humanized cellular immune system components with improved diversity of tcrβ repertoire
US20240099279A1 (en) 2022-09-22 2024-03-28 Regeneron Pharmaceuticals, Inc. Genetically modified mice expressing components of human cellular immune system

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